Cardiovascular & Hematological Agents in Medicinal Chemistry (Formerly Current Medicinal Chemistry - Cardiovascular & Hematological Agents) - Volume 21, Issue 3, 2023

Background: Several studies have shown that adipose-derived mesenchymal stem cells (AMSCs) can differentiate into mesenchymal lineages, including cardiac cell types, but complete differentiation into cardiomyocytes is challenging. Unfortunately, the optimal method to maximize AMSCs differentiation has not yet been established. Platelet-rich plasma (PRP), which contains rich growth factors, is believed to stimulate stem cell proliferation and differentiation in the context of cardiac tissue regeneration. Objective: This study aimed to analyze the effect of PRP administration to enhance the differentiation of AMSCs into cardiomyocytes. Methods: This study used a randomized post-test-only controlled group design. AMSCs were isolated from adipose tissues and cultured for 4 passages. The samples were divided into 3 groups, a negative control group (α-MEM), a positive control group (differentiation medium), and a treatment group (PRP). The assessment of GATA-4 expression was conducted using flow cytometry on day-5. The assessment of troponin expression was conducted using immunocytochemistry on day- 10. Data analysis was conducted using T-test and One-Way ANOVA. Results: Flowcytometry of GATA-4 expression revealed a significant improvement in PRP group compared to negative and positive control group (67.04 ± 4.49 vs. 58.15 ± 1.23 p < 0.05; 67.04 ± 4.49 vs. 52.96 ± 2.02 p < 0.05). This was supported by the results of immunocytochemistry on troponin expression, which revealed significant improvement in the PRP group compared to negative and positive controls (38.13 ± 5.2 vs. 10.73 ± 2.39 p < 0.05; 38.13 ± 5.2 vs. 26.00 ± 0.4 p < 0.05). Conclusion: PRP administration in the AMSCs culture could significantly improve the differentiation of AMSCs into cardiomyocytes measured by GATA-4 and troponin expressions. This was concordant with our hypothesis, which stated that there was an effect of PRP administration on AMSCs differentiation into cardiomyocytes.

Aims: The present work aimed to assess the antihypertensive activity of Salvia aucheri. Background: Salvia aucheri (S. aucheri) is an aromatic and medicinal herb belonging to the Lamiaceae family. In Morocco, this plant is locally used for used to treat stomach, digestive disorders, rheumatism, and hypertension. Nevertheless, the effect of Salvia aucheri on hypertension has not yet been studied. Objective: The objective of this investigation was to evaluate the beneficial effect of the aqueous extract of S. aucheri leaves on arterial blood pressure, systolic blood pressure (SBP), mean blood pressure (MBP), diastolic blood pressure (DBP), and heart rate (HR) in normotensive and hypertensive rats. In addition, the effect of the aqueous extract of S. aucheri leaves on vasodilatation was assessed in isolated rat aortic rings with functional endothelium precontracted with epinephrine EP or KCl. Methods: The aqueous extract of the aerial parts of S. aucheri (AESA) was obtained, and its antihypertensive ability was pharmacologically investigated in L-NAME hypertensive and normotensive rats. The rats received AESA orally at two selected doses of 100 and 140 mg/kg for six hours (acute experiment) and seven days (sub-chronic). Thereafter, systolic, diastolic, mean arterial blood pressure and heart rate were evaluated. Moreover, the vasorelaxant activity of AESA was performed in thoracic aortic ring rats. In addition, the mechanisms of action involved in the vasorelaxant effect were studied. Results: The results indicated that AESA significantly reduced the systolic, diastolic, and mean arterial blood pressure in hypertensive rats over both single and repeated oral administration. However, AESA did not change the blood pressure parameters in normotensive rats. Concerning the results of vasorelaxant activity, the results showed that AESA was able to provoke potent vasorelaxant ability, which seems to be mediated through direct nitric oxide (NO) and NO-cyclic guanosine monophosphate pathways. Conclusion: The study elucidates the beneficial action of AESA as an antihypertensive and vasorelaxant agent.

Background: Ammodaucus leucotrichus is a medicinal plant used in traditional medicine to treat various ailments, including hypertension. Aims: The study aimed to determine the antihypertensive activity of Ammodaucus leucotrichus. Objective: The study aimed to investigate the antihypertensive and vasorelaxant activities of the aqueous extract of Ammodaucus leucotrichus fruits (ALAE) in rats. Methods: ALAE was prepared to study its antihypertensive effect in L-NAME (Nω-L-arginine methyl ester)-induced hypertensive rats and its vasorelaxant activity in isolated thoracic aortas of rats. The acute and subchronic effects of ALAE on systolic, diastolic, mean arterial pressure, and heart rate (HR) were evaluated after oral administration of ALAE (60 and 100 mg/kg body weight) for 6 h for the acute experiment and over 7 days for the subchronic test. Isolated thoracic aortic rings were prepared to examine the vasorelaxant action of ALAE. Several common pharmacological agents were used to test potential pathways implicated in vasorelaxant action. Results: The results showed that ALAE reduced blood pressure parameters (systolic, mean, and diastolic blood pressure) in L-NAME-induced hypertension rats after repeated oral treatment over seven days without affecting normotensive rats. Furthermore, in thoracic aortic rings pre-contracted with epinephrine (EP) (10 μM) or KCl (80 mM), ALAE (0.250-1.625 mg/ml) showed a vasorelaxant effect. In isolated rat thoracic aortas, blockage of soluble guanylyl cyslase with blue methylene (P < 0.01) partially decreased this vasorelaxant effect. In addition, blockage of the prostaglandin synthesis pathway with indomethacin (P<0.05) also reduced the vasorelaxant activity of ALAE. Pretreatment of aortic rings with glibenclamide, propanolol, L-NAME, MLN-4760, or nifedipine did not affect ALAE-induced vasorelaxation. Conclusion:Ammodaucus leucotrichus is a prescient medicinal plant, able to act as an antihypertensive agent. Moreover, the results suggest that the extract increased cGMP in NO-independent manner.

Background/Aim: Infections are a major cause of morbidity and mortality in children with haematologic malignancies and solid tumors as well as those undergoing hematopoietic stem cell transplantation (HSCT). The purpose of our study was to record the epidemiological characteristics and outcomes of bacteremias, focusing on pathogens, as well as risk factors and mortality rates in patients of a pediatric hematology-oncology unit from Northern Greece. Materials and Methods: A retrospective analysis was conducted, which included all positive blood cultures from pediatric hematology oncology patients aged from 1 to 16 years old admitted to the Pediatric and Adolescent Hematology Oncology Unit of AHEPA University Hospital of Thessaloniki between January 2014 and December 2018. Data were collected from patients’ printed and electronic medical records. Results: 73 episodes of bacteremias were identified (41% male and 32% female with a ratio of 1.28:1; median age 6.5 years; 13.7% solid tumor, 72.6% acute lymphoblastic leukemia, 13.7% acute myeloid leukemia, and 95.8% with an indwelling permanent catheter). 49.3% of the isolates were Gram-positive bacteria and 50.7% Gram-negative, and the ratio of Gram-negative to Grampositive was 1.02. Coagulase-negative staphylococci were most frequent (39.7%), followed by E. coli (17.8%) and Klebsiella pneumoniae (17.8%). Out of all Gram-negatives, 13.5% carbapenemase producers and 8.1% ESBL-producers were found. In relation to Gram-positive, 79.3% were identified as methicillin-resistant CoNS. During the study period, 10.9% of indwelling catheters were removed, and 2.73% of episodes resulted in ICU transfer. The 3-month mortality rate was 8.2%. Conclusion: This study demonstrated an almost equal distribution of Gram-positive and Gramnegative bacteremias in total in this population but with an increase in the isolation of Grampositive bacteria over the last years, which is consistent with other similar studies in this patient group. Knowledge of the local epidemiology and bacterial antimicrobial resistance is important to prevent and timely treat these life-threatening infections in immunocompromised pediatric oncology patients.

Aims: The aim of the study was to investigate the antihypertensive effect of L-Tartaric acid. Background: L-Tartaric acid (L-TA) is a well-known weak organic acid that naturally occurs in a wide range of fruits, most notably in grapes, tamarind, and citrus. Objective: The present study aimed to assess the effect of acute and subchronic administration of L-TA on blood pressure parameters in normotensive and hypertensive rats as well as its vasorelaxant potency. Methods: In the current study, the antihypertensive activity of L-TA was pharmacologically studied. L-NAME-induced hypertensive and normotensive rats received L-TA (80 and 240 mg/kg) orally over six hours for the acute experiment and seven days for the subchronic treatment. Thereafter, systolic, diastolic, mean, mid arterial blood pressure, and pulse pressure as well as heart rate were evaluated. In the in vitro experiment, the vasorelaxant ability of L-TA was performed in ratisolated thoracic aorta. Results: An important drop in blood pressure was recorded in L-NAME-induced hypertensives treated with L-TA. This molecule also produced a dose-dependent relaxation of the aorta precontracted with norepinephrine (NEP) and KCl. The study demonstrated that the vasorelaxant capacity of L-TA seems to be exerted through the activation of eNOS/NO/cGMP pathways.

Aims: The study aimed to investigate the effect of Euphorbia cheiradenia on blood pressure. Background: Euphorbia cheiradenia is a medicinal plant with several medicinal properties. Objective: This study aimed to study the vasorelaxant and antihypertensive capacity of the aqueous extract of Euphorbia cheiradenia (E. cheiradenia), and to evaluate its effect on angiotensinconverting enzyme 2 (ACE2). Methods: The antihypertensive ability of aerial parts of the aqueous extract of E. cheiradenia (AEEC) was investigated in L-NAME-induced hypertensive rats, and its vasorelaxant effect was performed on the isolated thoracic rat aorta. In addition, the possible inhibitory effect of AEEC on ACE2 was also studied. Results: AEEC lowered blood pressure parameters in hypertensive rats. The study of the vasorelaxant activity revealed that AEEC partially relaxed the aortic rings through activation of the KATP channel and inhibition of the β-adrenergic pathway. Whereas pretreatment of aortic rings with nifedipine, indomethacin, L-NAME, and methylene blue did not attenuate AEEC-induced vasorelaxation. However, AEEC did not affect ACE2 in isolated rat aortas. Conclusion: The study showed that aqueous E. cheiradenia extract exhibits significant antihypertensive activity in hypertensive rats.

Background: Acute myocardial infarction (AMI) pathophysiology is mediated by systemic, intraplaque myocardial inflammatory processes that occur mainly due to coronary artery thrombosis in an atherosclerotic plaque area. The G-protein-coupled chemokine receptor (Ccr6) is displayed on the surface of many types of leukocytes, that have been found in atherosclerotic plaques. It is a novel mediator of inflammation and immune response. Objectives: To determine CCR6 lymphocyte expression in AMI patients and its association with disease severity using the Gensini scoring system. Methods: 25 AMI patients and 25 controls underwent flow cytometry to determine the percentage of circulating CCR6+ lymphocytes. To forecast AMI and determine how CCR6 expression relates to it, multivariate logistic regression analysis was used. Results and Discussion: There was a higher percentage of CCR6+ lymphocyte expression in AMI patients than in controls. In addition, CCR6 showed a significant positive correlation with the Gensini score (GS) in the AMI group then with the degree of coronary artery disease (CAD). Conclusion: The chemokine receptor CCR6 is an independent biomarker for AMI and mayplay a role as a mediator of T lymphocyte recruitment, which is associated with coronary lesion destabilization.

Objective: Salvia miltiorrhiza (SM) contains four major aqueous active ingredients, which have been isolated, purified and identified as danshensu (DSS), salvianolic acid A (Sal-A), salvianolic acid B (Sal-B) and protocatechuic aldehyde (PAL), A mixture of these four ingredients is called SABP. Although aqueous extract from Salvia miltiorrhiza has been traditionally used to treat cardiovascular diseases, the efficacy and function of the optimal ratio of SABP in preventing and treating cardiovascular diseases remain unknown. This study aims to explore the antiinflammatory mechanisms underlying the attenuation of atherosclerosis development by aqueous extract from Salvia miltiorrhiza. Methods: Male ApoE^-/- mice (6 weeks) were randomly allocated into three groups: the model group (Model), the SABP group (SABP), and the rosuvastatin calcium group (RC). Male C57BL/6 mice (6 weeks) were used as a control group. All mice were fed with an ordinary diet. After 8 weeks of treatment, the lipid profiles in serum and the lactate dehydrogenase (LDH) and creatine kinase (CK) in heart tissue were measured using an automatic biochemical analyzer. Alterations of the thoracic aorta and the heart were assessed using Hematoxylin and eosin staining. The protein expression of Toll-like receptor 4 (TLR4), TGF beta-activated kinase 1 (TAK1), nuclear factor kappa-B (NF-ΚB), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the heart tissue were determined though immunohistochemistry and western blotting analysis. Results: The serum low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and total cholesterol (TC) levels were increased, and the high-density lipoprotein cholesterol (HDL-C) level was decreased in ApoE^-/- mice. SABP significantly decreased serum lipid levels and improved histopathology in the thoracic aorta. In addition. SABP treatment inhibited the expression of TLR4, TAK1, NF-ΚB, IL-6 and TNF-α in the heart in ApoE^-/- mice. The LDH and CK in the heart did not differ significantly among different groups, and the heart did not have obvious pathological changes. Conclusion: These findings indicated that SABP may exert an anti-atherosclerotic effect by lowering blood lipids and inhibiting inflammatory response via TLR4/ NF-ΚB signaling pathway.